Reliable biomarkers in renal cell carcinoma (RCC) remain elusive. While several markers have been shown to be associated with prognosis, and may aid in risk assessment, predictive biomarkers of response to immune checkpoint inhibitors (ICIs) have not been established. Previous studies have shown that a high pretreatment neutrophil-lymphocyte ratio (NLR) is a negative prognostic factor in RCC. However, a clinically useful cut-off for the predictive and prognostic value of NLR has not been well defined. We conducted a retrospective analysis of 132 patients with previously untreated metastatic clear cell RCC (ccRCC) who received first line ICI-based therapy. ICI-based therapy included anti-PD-1/PD-L1 alone or in combination with anti-CTLA-4 or VEGF-TKI. Platelet, haemoglobin, neutrophil and lymphocyte counts were collected prior to treatment and at 12-weeks after treatment initiation. Radiologic response at 12-weeks and overall survival (OS) data was also collected. Low haemoglobin, high platelet count, and NLR ≥3 were statistically significant negative predictive biomarkers when assessed at 12-weeks, but not at baseline. Median OS was shorter in patients with low haemoglobin (20.3 months vs. 51.6 months, = .009), high platelet count (14.3 months vs. 43.8 months, = .003), and NLR ≥ 3 (17.5 months vs. 40.3 months, < .001) at 12-weeks. In an IMDC-risk adjusted analysis, only NLR ≥3 at 12-weeks remained statistically significant (OR of 2.11, = .003) A dynamic change towards lower absolute NLR overtime was associated with longer OS. In patients who had baseline NLR ≥ 3, those who achieved NLR < 3 at 12-weeks demonstrated significant longer median OS compared to those whose NLR remained persistently ≥ 3 (40.3 months vs. 14.7 months, = .004). NLR ≥3, low haemoglobin and elevated platelet count after 12-weeks of ICI-based first line therapy were negatively prognostic and predictive in patients with metastatic RCC. Normalization of NLR in patients with baseline elevation was associated with longer median OS and response to therapy. These results suggest that monitoring of routine haematologic biomarkers during therapy may provide important predictive and prognostic information, beyond what is available with baseline risk assessment scoring systems.

中文翻译：

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作为免疫检查点抑制剂治疗转移性肾细胞癌的预测和预后生物标志物，NLR 优于低血红蛋白和高血小板计数

肾细胞癌（RCC）的可靠生物标志物仍然难以捉摸。虽然多种标记物已被证明与预后相关，并且可能有助于风险评估，但免疫检查点抑制剂 (ICIs) 反应的预测生物标记物尚未建立。先前的研究表明，治疗前较高的中性粒细胞-淋巴细胞比率（NLR）是肾细胞癌的负面预后因素。然而，NLR 的预测和预后价值的临床有用临界值尚未明确定义。我们对 132 名既往未经治疗的转移性透明细胞肾细胞癌 (ccRCC) 患者进行了回顾性分析，这些患者接受了一线 ICI 治疗。基于 ICI 的治疗包括单独抗 PD-1/PD-L1 或联合抗 CTLA-4 或 VEGF-TKI。在治疗前和治疗开始后 12 周收集血小板、血红蛋白、中性粒细胞和淋巴细胞计数。还收集了 12 周时的放射学反应和总生存 (OS) 数据。在 12 周评估时，低血红蛋白、高血小板计数和 NLR ≥3 是具有统计学意义的阴性预测生物标志物，但在基线时则不然。低血红蛋白患者（20.3 个月 vs. 51.6 个月，= .009）、高血小板计数患者（14.3 个月 vs. 43.8 个月，= .003）和 NLR ≥ 3（17.5 个月 vs. 40.3 个月， < .001) 在 12 周时。在 IMDC 风险调整分析中，只有 12 周时 NLR ≥3 仍具有统计学显着性（OR 为 2.11，= .003） 随着时间的推移，绝对 NLR 降低的动态变化与更长的 OS 相关。在基线 NLR ≥ 3 的患者中，与 NLR 持续≥ 3 的患者相比，在 12 周达到 NLR < 3 的患者的中位 OS 显着更长（40.3 个月 vs. 14.7 个月，= .004）。在基于 ICI 的一线治疗 12 周后，NLR ≥3、低血红蛋白和升高的血小板计数对转移性 RCC 患者具有负面预后和预测作用。基线升高的患者 NLR 正常化与较长的中位 OS 和治疗反应相关。这些结果表明，在治疗期间监测常规血液生物标志物可以提供重要的预测和预后信息，超出基线风险评估评分系统所能提供的信息。